The effects of a motorized passive simulated jogging device on descent of the arterial pulse waveform dicrotic notch: A single arm placebo‐controlled cross‐over trial

Abstract Whole Body Periodic Acceleration (WBPA, pGz), is a bed that moves the body headward to forward, adds pulses to the circulation inducing descent of the dicrotic notch (DN) on the pulse waveform with an increase in a/b ratio (a = the height of the pulse waveform and b = the height of the secondary wave). Since the WBPA is large, heavy, and non‐portable, we engineered a portable device (Jogging Device, JD). JD simulates passive jogging and introduces pulsations to the circulation. We hypothesized that JD would increase the a/b ratio during and after its use. In Study A, a single‐arm placebo‐controlled cross‐over trial was conducted in24 adults (53.8 ± 14.4 years) using JD or control (CONT) for 30 min. Blood pressure (BPs and BPd) and photoplethysmograph pulse (a/b) were measured at baseline (BL), during 30 min of JD or CONT, and 5 and 60 min after. In Study B (n = 20, 52.2 ± 7 years), a single‐arm observational trial of 7 consecutive days of JD on BP and a/b, measured at BL, and after 7 days of JD and 48 and 72 hr after its discontinuation. In Study A, BPs, and BPd decreased during JD by 13% and 16%, respectively, while in CONT both increased by 2% and 2.5%, respectively. The a/b increased by 2‐fold and remained greater than 2‐fold at all‐time points, with no change in a/b during CONT. In Study B, BPs and BPd decreased by 9% and remained below BL, at 72 hr after discontinuation of JD. DN descent also occurred after 7 days of JD with a/b increase of 80% and remained elevated by 60% for at least 72 h. JD improves acute and longer‐term vascular hemodynamics with an increase in a/b, consistent with increased effects of nitric oxide (NO). JD may have significant clinical and public health implications.


Day 3
Legend: Recruitment of study subjects was done from a larger protocol ClinicalTrials.gov (NCT03426774). All subjects were studied in the seated posture. On Day 1 subjects were randomized to JD or Control (CONT). On Day 3 subjects were crossed over to receive JD if they started day 1 in CONT, or to CONT if they started day1 on JD. Continuous non-invasive arterial blood pressure (CNAP) and pulse waveform from finger plethysmograph were continuously collected. Measurements of arterial blood pressure and descent of the dicrotic notch (a/b) on the pulse waveform were analyzed after 10 min of quiet sitting (Baseline, BL). The Jogging Device (JD) was begun at a frequency of 190 steps in place. Blood pressure and pulse waveform were analyzed after 5,10,20,30 min of the JD or CONT (T5,T10,T20,T30), and after 5 and 60 min after discontinuation of the JD or CONT (Recovery, REC 5, REC 60). 3

CONSORT FLOW DIAGRAM
Legend: Twenty-four subjects were enrolled and randomized (using random choice generator*) on day 1 to CONT or JD and crossed over on day 3. No subjects were excluded and all 24 subjects analyzed.

Study B: Effects of 7 day use of JD on Blood Pressure and DN position An Observational Trial
Legend: Recruitment of study subjects was performed from a larger ClinicalTrials.gov ClinicalTrials.gov protocol (NCT03550105). All subjects were studied in seated posture. On day 1, after 10 min of quiet sitting baseline (BL), continuous noninvasive arterial blood pressure (CNAP) and pulse waveform from finger plethysmograph were continuously collected. The subjects were then instructed on the use of the Jogging Device (JD) and instructed to use it at least three times per day for 30 minutes for 7 days (JD7). CNAP and the pulse waveform of the finger plethysmograph were again measured on JD7 and 48 and 72 hours after discontinuation of JD. To replicate real-world behavior, subjects were told to continue their current schedule, diet, and physical activity.

Consort Flow Diagram Study B
Participant Recruitment

Study B: Effects of 7 day use of JD on Blood Pressure and DN position An Observational Trial
Legend: Twenty subjects were recruited as part of a larger ClinicalTrials.gov protocol (NCT03550105), ages 18-80. Subjects were instructed on the use of the Jogging Device (JD) and instructed to use it at least three times per day for 30 min each session for 7 days (JD7). Three follow-up visits were made in which continuous noninvasive arterial pressure and plethysmographic pulse waveform were measured. There were no excluded subjects and none were lost to follow-up. All subjects were included in the analysis.

Introduction
Background and objectives 2a Scientific background and explanation of rationale 5 2b Specific objectives or hypotheses 6

Methods
Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio 6-8 and ESM 3b Important changes to methods after trial commencement (such as eligibility criteria), with reasons N/A Participants 4a Eligibility criteria for participants 7 4b Settings and locations where the data were collected 7-8 Interventions 5 The interventions for each group with sufficient details to allow replication, including how and when they were actually administered 8 and ESM

Outcomes 6a
Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed 8 6b Any changes to trial outcomes after the trial commenced, with reasons N/A Sample size 7a How sample size was determined 9 7b When applicable, explanation of any interim analyses and stopping guidelines N/A Randomisation: Sequence generation 8a Method used to generate the random allocation sequence N/A 8b Type of randomisation; details of any restriction (such as blocking and block size) N/A Allocation concealment mechanism 9 Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned N/A Implementation 10 Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions N/A Blinding 11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) N/A 11b If relevant, description of the similarity of interventions N/A Statistical methods 12a Statistical methods used to compare groups for primary and secondary outcomes 9 12b Methods for additional analyses, such as subgroup analyses and adjusted analyses 9

Legend:
Categories for the percent change from the baseline of the dicrotic notch (a/b) on the pulse waveform for Study A (Acute Effects of JD on Blood Pressure and DN position) and Study B ((Effects of 7-day use of JD on Blood Pressure and DN position baseline). The percent change for Study A was calculated from the difference between BL and after 30 min of JD (Jogging device, T30). The percent change for Study B was calculated from the difference between BL and 7 days of JD (JD7). The categories are less than 49% change (< 49%) to more than 100% (> 100%) change. In each category, the actual number of study subjects followed by the percent (actual number/study n). In study A, 79% of the study participants had a greater than 50% change in a/b. In Study B, 85% of the study participants had a greater than 50% change in a/b.  Legend: Participant's Characteristics of the participant of the participant for Study A ; Gender (M=male, F=Female), Age Range in years, and percent change in the a / b category in response to JD (less than 49% change < 49%, 50-100% change and > 100% change). Note 79% (19/24 ) subjects had a greater than 50% change in a/b from baseline in response to JD.